title: Major molecular response during the first year of dasatinib, imatinib or nilotinib treatment for newly diagnosed chronic myeloid leukemia: a network meta-analysis.
abstract: OBJECTIVE
  No randomized trials have directly compared dasatinib with nilotinib for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase. The objective of this study was to indirectly compare these therapies using evidence from randomized trials versus imatinib, the current standard of care.
  
  
  METHODS
  Randomized trials that included either dasatinib or nilotinib as first-line treatment for chronic myeloid leukemia were identified in a systematic review. Inclusion and exclusion criteria, baseline characteristics and endpoint definitions were compared across trials. The outcome of interest was major molecular response by or at 12 months. A network meta-analysis was conducted to compare rates of major molecular response among therapies while adjusting for measurement of response by or at 12 months.
  
  
  RESULTS
  One trial of nilotinib versus imatinib (ENESTnd) and two trials of dasatinib versus imatinib (DASISION and the S0325 Intergroup Trial) were identified. Major molecular response was reported by and at 12 months in ENESTnd, by 12 months in DASISION, and at 12 months in the S0325 Intergroup Trial. In the network meta-analysis, nilotinib had a 97% chance of having the highest rate of major molecular response compared to dasatinib and imatinib, corresponding to absolute rates of major molecular response by month 12 of 55.2%, 44.8% and 26.7%, respectively.
  
  
  CONCLUSIONS
  In this network meta-analysis, nilotinib was associated with the highest rate of major molecular response, compared to dasatinib and imatinib, during the first year of treatment in patients with newly diagnosed chronic myeloid leukemia in the chronic phase.
authors.affiliation: Analysis Group, Inc., Boston, MA 02199, USA. Electronic address: jsignorovitch@analysisgroup.com.
authors.forename: James
authors.initials: J
authors.lastname: Signorovitch
authors.forename: Rajeev
authors.initials: R
authors.lastname: Ayyagari
authors.forename: William M
authors.initials: WM
authors.lastname: Reichmann
authors.forename: Eric Q
authors.initials: EQ
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use; D000069439:Dasatinib; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods*; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib; D000069439:Dasatinib
keywords: Chronic myeloid leukemia; Comparative effectiveness; Dasatinib; Imatinib; Major molecular response; Network meta-analysis; Nilotinib